Fatty Acid Binding Proteins from Different Tissues Show Distinct Patterns of Fatty Acid Interactions

• Published in: Biochemistry (Easton) 2000-06, Vol.39 (24), p.7197-7204
• Main Authors: Richieri, Gary V, Ogata, Ronald T, Zimmerman, Aukje W, Veerkamp, Jacques H, Kleinfeld, Alan M
• Format: Article
• Language: English
• Subjects: Animals; Carrier Proteins - metabolism; Chromatography, High Pressure Liquid; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; Fatty Acids - metabolism; Humans; Intestinal Mucosa - metabolism; Liver - metabolism; Myelin P2 Protein - metabolism; Myelin Sheath - metabolism; Myocardium - metabolism; Neoplasm Proteins; Nerve Tissue Proteins; Protein Binding; Rats; Receptors, Retinoic Acid - metabolism; Thermodynamics; Tumor Suppressor Proteins
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi000314z

Fatty acid binding proteins (FABP) form a family of proteins displaying tissue-specific expression. These proteins are involved in fatty acid (FA) transport and metabolism by mechanisms that also appear to be tissue-specific. Cellular retinoid binding proteins are related proteins with unknown roles in FA transport and metabolism. To better understand the origin of these tissue-specific differences we report new measurements, using the acrylodated intestinal fatty acid binding protein (ADIFAB) method, of the binding of fatty acids (FA) to human fatty acid binding proteins (FABP) from brain, heart, intestine, liver, and myelin. We also measured binding of FA to a retinoic acid (CRABP-I) and a retinol (CRBP-II) binding protein and we have extended to 19 different FA our characterization of the FA−ADIFAB and FA−rat intestinal FABP interactions. These studies extend our previous analyses of human FABP from adipocyte and rat FABPs from heart, intestine, and liver. Binding affinities varied according to the order brain ≈ myelin ≈ heart > liver > intestine > CRABP > CRBP. In contrast to previous studies, no protein revealed a high degree of selectivity for particular FA. The results indicate that FA solubility (hydrophobicity) plays a major role in governing binding affinities; affinities tend to increase with increasing hydrophobicity (decreasing solubility) of the FA. However, our results also reveal that, with the exception of the intestinal protein, FABPs exhibit an additional attractive interaction for unsaturated FA that partially compensates for their trend toward lower affinities due to their higher aqueous solubilities. Thermodynamic potentials were determined for oleate and arachidonate binding to a subset of the FABP and retinoid binding proteins. FA binding to all FABPs was enthalpically driven. The ΔH° values for paralogous FABPs, proteins from the same species but different tissues, reveal an exceptionally wide range of values, from −22 kcal/mol (myelin) to −7 kcal/mol (adipocyte). For orthologous FABPs from the same tissue but different species, ΔH° values were similar. In contrast to the enthalpic dominance of FA binding to FABP, binding of FA to CRABP-I was entropically driven. This is consistent with the notion that FA specificity for FABP is determined by the enthalpy of binding. Proteins from different tissues also revealed considerable heterogeneity in heat capacity changes upon FA binding, ΔCp values ranged between 0 and −1.3 kcal mol-1 K-1.